19-36818816-C-T

Variant names:

• chr19-36818816-C-T
• rs139458377
• NM_206894.4:c.1528G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_206894.4(ZNF790):​c.1528G>A​(p.Glu510Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E510Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF790 NM_206894.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 1 publications found

Genes affected

ZNF790 (HGNC:33114): (zinc finger protein 790) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF790-AS1 (HGNC:27617): (ZNF790 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17439973).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206894.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF790	NM_206894.4	MANE Select	c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	NP_996777.2	Q6PG37
	ZNF790	NM_001242800.2		c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	NP_001229729.1	Q6PG37
	ZNF790	NM_001242801.2		c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	NP_001229730.1	Q6PG37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF790	ENST00000356725.9	TSL:2 MANE Select	c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	ENSP00000349161.3	Q6PG37
	ZNF790	ENST00000613249.4	TSL:4	c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	ENSP00000480764.1	Q6PG37
	ZNF790	ENST00000614179.4	TSL:3	c.1528G>A	p.Glu510Lys	missense	Exon 5 of 5	ENSP00000480834.1	Q6PG37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	N
PhyloP100		-0.15
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.070
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.041	D
Polyphen		0.46	P
Vest4		0.22
MutPred		0.55		Gain of methylation at E510 (P = 6e-04)
MVP		0.57
MPC		0.30
ClinPred		0.74	D
GERP RS		3.0
Varity_R		0.16
gMVP		0.057
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139458377; hg19: chr19-37309718;